GLIS3 Gene (GLIS Family Zinc Finger 3)
Transcriptional regulator in pancreatic development, thyroid function, and glucose homeostasis
Gene Information Card
| Symbol | GLIS3 |
|---|---|
| Full Name | GLIS family zinc finger 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p24.2 |
| NCBI Gene ID | 169792 ncbi.nlm.nih.gov/gene/169792 |
| Ensembl ID | ENSG00000107249 |
| UniProt ID | Q8NEA6 |
| OMIM ID | 610192 |
| HGNC ID | 24825 |
| Aliases | ZNF515, KIAA1237, NDH1 |
Description
GLIS3 encodes a member of the GLI-similar zinc finger protein family, functioning as a transcriptional activator and repressor. It plays a critical role in pancreatic beta-cell development, insulin gene expression, thyroid morphogenesis, and glucose homeostasis. Mutations in GLIS3 cause neonatal diabetes mellitus with congenital hypothyroidism (NDH syndrome) and are associated with increased risk of type 1 and type 2 diabetes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neonatal diabetes mellitus with congenital hypothyroidism (NDH syndrome) | Loss-of-function mutations impair GLIS3-mediated transcription of insulin and thyroid-related genes, leading to pancreatic beta-cell dysfunction and thyroid agenesis/hypoplasia. | OMIM #610199; ClinVar |
| Type 1 diabetes | GLIS3 variants (e.g., rs7020673) modulate autoimmune susceptibility and beta-cell survival. | GWAS; PMID: 24509480 |
| Type 2 diabetes | GLIS3 intronic variants (e.g., rs7041847) affect insulin secretion and glucose homeostasis. | GWAS; PMID: 22885923 |
| Congenital hypothyroidism | GLIS3 mutations disrupt thyroid follicular cell differentiation and thyroid hormone synthesis. | OMIM #610199; PMID: 17327417 |
| Polycystic kidney disease | GLIS3 deficiency leads to renal cyst formation in mouse models, but human evidence limited. | PMID: 23994610 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Thyroid | 8.3 | Medium |
| Kidney | 5.1 | Low |
| Liver | 2.4 | Low |
| Testis | 1.8 | Low |
| Brain | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta-cell) | 15.2 | High expression; insulin promoter activation |
| MIN6 (mouse beta-cell) | 14.8 | High expression; glucose-responsive |
| HEK293 | 2.1 | Low endogenous; used for overexpression studies |
| HeLa | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.208C>T (p.Arg70*) | Nonsense | Rare | Loss of function; truncation of zinc finger domains; NDH syndrome |
| c.1033C>T (p.Arg345Cys) | Missense | Rare | Impaired DNA binding; reduced transcriptional activity |
| c.1390G>A (p.Gly464Arg) | Missense | Rare | Disrupted nuclear localization; dominant-negative effect |
| c.1681delC (p.Leu561Trpfs*12) | Frameshift | Rare | Premature stop; complete loss of function |
| rs7020673 (intronic) | SNP | Common (MAF 0.35) | Risk allele for type 1 diabetes; alters enhancer activity |
Mutation functional classification
Loss of Function (LOF)
Most GLIS3 mutations (nonsense, frameshift, missense in zinc finger domains) result in loss of transcriptional activation of target genes (e.g., insulin, PAX8, NKX2-1), leading to NDH syndrome.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in human disease.
Dominant Negative (DN)
Missense mutations in the C-terminal domain (e.g., p.Gly464Arg) can interfere with wild-type GLIS3 function, causing dominant-negative effects in vitro.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin secretion pathway (Reactome: R-HSA-422085)
• Transcriptional regulation of pancreatic beta-cell development (KEGG: hsa04950)
• Thyroid hormone synthesis (KEGG: hsa04918)
• GLI/GLIS signaling network (PMID: 23994610)
Protein Summary
GLIS3 is a 930-amino-acid nuclear protein containing five C2H2-type zinc finger domains that mediate sequence-specific DNA binding to GLIS response elements (GREs). It functions as both a transcriptional activator (e.g., insulin, PAX8) and repressor (e.g., HES1). The protein is essential for pancreatic beta-cell maturation, insulin gene transcription, thyroid follicular cell differentiation, and kidney development. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLIS3 Knockout HEK293 Cell Line | EDJ-KQ2274 | Human | 169792 | Details Get a Quote |
| GLIS3 Knockout A-549 Cell Line | EDJ-KQ22618 | Human | 169792 | Details Get a Quote |
| GLIS3 Knockout HCT 116 Cell Line | EDJ-KQ22619 | Human | 169792 | Details Get a Quote |
| GLIS3 Knockout HeLa Cell Line | EDJ-KQ22620 | Human | 169792 | Details Get a Quote |
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